The DOI matches its Crossref record; 233 of the 233 references it cites were found in a registry or an index.
Polydrug abuse: A review of opioid and benzodiazepine combination use
Open accessAbstract
This paper reviews studies examining the pharmacological interactions and epidemiology of the combined use of opioids and benzodiazepines (BZDs). A search of English language publications from 1970 to 2012 was conducted using PubMed and PsycINFO(®). Our search found approximately 200 articles appropriate for inclusion in this paper. While numerous reports indicate that the co-abuse of opioids and BZDs is ubiquitous around the world, the reasons for the co-abuse of these medications are not entirely clear. Though the possibility remains that opioid abusers are using BZDs therapeutically to self-medicate anxiety, mania or insomnia, the data reviewed in this paper suggest that BZD use is primarily recreational. For example, co-users report seeking BZD prescriptions for the purpose of enhancing opioid intoxication or "high," and use doses that exceed the therapeutic range. Since there are few clinical studies investigating the pharmacological interaction and abuse liability of their combined use, this hypothesis has not been extensively evaluated in clinical settings. As such, our analysis encourages further systematic investigation of BZD abuse among opioid abusers. The co-abuse of BZDs and opioids is substantial and has negative consequences for general health, overdose lethality, and treatment outcome. Physicians should address this important and underappreciated problem with more cautious prescribing practices, and increased vigilance for abusive patterns of use.
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“patients who use BZDs and have co-occurring alcohol use disorder (AUD) or OUD are at higher risk of morbidity and mortality because of the cross-tolerance and combined CNS and respiratory depressant effects of these substances.23,52”
From Joint Clinical Practice Guideline on Benzodiazepine Tapering: Considerations When Risks Outweigh Benefits (2025) · cites this paper as [52]
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“Combined use of BZDs and opioids increases the risk of adverse events, including fatal and nonfatal overdose, due to the CNS depression caused by both medication classes (see “Patients Co-prescribed Benzodiazepines and Opioids” for further discussion).7,23,52”
From Joint Clinical Practice Guideline on Benzodiazepine Tapering: Considerations When Risks Outweigh Benefits (2025) · cites this paper as [52]
In the citing paper
“Opioids and benzodiazepines were found to be co-abused by opioid users to enhance opioid intoxication (Jones et al., 2012).”
From National trends in pharmaceutical opioid related overdose deaths compared to other substance related overdose deaths: 1999-2009. (2013) · cites this paper as Jones et al., 2012
In the citing paper
“Previous research has also demonstrated that benzodiazepines have greater misuse liability among those with histories of alcohol use disorder (23) and increase the reinforcing effects of opioids when they are taken in combination (24)”
From Prevalence and correlates of the misuse of z-drugs and benzodiazepines in the National Survey on Drug Use and Health (2023) · cites this paper as [24]
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The epidemiology of benzodiazepine misuse: A systematic review*
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Brandt, J., & Leong, C. (2017) · Drugs in R&D · doi:10.1007/s40268-017-0207-7 · Cited by 356
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Emotion Regulation and Substance Use: A Meta-Analysis
Weiss, N. H., Kiefer, R., Goncharenko, S., Raudales, A. M., Forkus, S. R., Schick, M. R., & Contractor, A. A. (2022) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2021.109131 · Cited by 235
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Psychosocial interventions for benzodiazepine harmful use, abuse or dependence
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“7,23,52 Excessive sedation has been observed when BZDs have been used with CYP3 A4 inhibitors, such as antibiotics like clarithromycin and erythromycin.”
Franklyn, A. M., Eibl, J. K., Gauthier, G., Pellegrini, D., Lightfoot, N. E., & Marsh, D. C. (2017) · Harm Reduction Journal · doi:10.1186/s12954-017-0134-5 · Cited by 39
McHugh, R. K., Votaw, V. R., Trapani, E. W., & McCarthy, M. D. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1129447 · Cited by 38
“Previous research has also demonstrated that benzodiazepines have greater misuse liability among those with histories of alcohol use disorder (23) and increase the reinforcing effects of opioids when they are taken in combination (24), consistent with our findings that those with benzodiazepine misuse had higher rates…”
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Metadata
- Authors
- Jones, J. D., Mogali, S., & Comer, S. D.
- Affiliations
- Columbia University (US)
- Corresponding author
- Comer, Sandra D.
- Venue
- Drug and Alcohol Dependence
- Publisher
- Elsevier BV
- Published
- 2012-09
- Volume
- 125
- Issue
- 1-2
- Pages
- 8-18
- ISSN
- 0376-8716 (ISSN-L)
- PMC
- PMC3454351
- OpenAlex
- W1975817655
- Cited by
- 703
- References
- 233
- Citations by year
- 2026: 26 · 2025: 26 · 2024: 52 · 2023: 45 · 2022: 58 · 2021: 63 · 2020: 88 · 2019: 65 · 2018: 67 · 2017: 64 · 2016: 59 · 2015: 39 · 2014: 32 · 2013: 16 · 2012: 1
- FWCI
- 4.34
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Drug and Alcohol Dependence (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (DA-09236, DA031022, R01DA022222, R01DA016759, P50DA009236, K01DA030446, DA016759, DA030446-01A, DA022222, R01DA031022, T32DA007294)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Forensic Toxicology and Drug Analysis
- Keywords
- polydrug abuse, opioid-benzodiazepine combination, benzodiazepine misuse, opioid abuse, drug interactions, recreational drug use, self-medication, drug overdose, prescribing patterns, abuse liability
- MeSH terms
- Analgesics, Opioid, Benzodiazepines, Drug Interactions, Humans, Opioid-Related Disorders, Substance-Related Disorders
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